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Biomedical subjects

J Reinhardt

Publications and source records attributed to J Reinhardt.

At least 37 records · Page 2Linked to original sources
PubMed1998

Migrating transformed MDCK cells are able to structurally polarize a voltage-activated K+ channel.

Cell migration of transformed renal epithelial cells (MDCK-F) depends-in addition to cytoskeletal mechanisms-on the polarized activity of a Ca2+-sensitive K+ channel in the rear part of the cells. However, because of the lack of specific markers for this channel we are not able to determine whether a polarized distribution of the channel protein underlies its functional polarization. To determine whether the migrating MDCK-F cells have retained the ability to target K+ channels to distinct membrane areas we stably transfected the cells with the voltage-dependent K+ channel Kv1.4. Stable expression and insertion into the plasma membrane could be shown by reverse transcription-PCR, genomic PCR, Western blot, and patch-clamp techniques, respectively. The distribution of Kv1.4 was assessed with indirect immunofluorescence by using conventional and confocal microscopy. These experiments revealed that Kv1.4 is expressed only in transfected cells where it elicits the typical voltage-dependent, rapidly inactivating K+ current. The Kv1.4 protein is clustered at the leading edge of protruding lamellipodia of migrating MDCK-F cells. This characteristic distribution of Kv1.4 provides strong evidence that migrating MDCK-F cells are able to insert ion channels into the plasma membrane in an asymmetric way, which reflects the polarization of migrating cells in the plane of movement. These findings suggest that not only epithelial cells and nerve cells, but also migrating cells, can create functionally distinct plasma membrane areas.

Animals↗
PubMed1998

Effect of black tea on azoxymethane-induced colon cancer.

Two sets of experiments on the role of tea in azoxymethane (AOM) induced colon cancer were performed. The first test involved male F344 rats given 1.25% solutions of black tea beginning at 5 weeks of age and ending at 51 days of age. At 6 and 7 weeks of age, they received 15 mg/kg AOM and were held for 50 weeks. Another group received the AOM dosage at 6 and 7 weeks and were placed on the tea solutions 2 days after the last AOM dosage, at 51 days of age, and held for the 50-week period. The end point was the occurrence and multiplicity of colon cancer, classified as in situ, exophytic, invasive and Peyer's patch carcinomas. Tea failed to affect the incidence and multiplicity of colon cancers when given during or after the AOM administration, but tea after AOM increased the multiplicity of exophytic carcinomas. In a second series of tests, solutions of 0.6, 1.25, 1.75 or 2.5% tea were given, beginning 1 week prior to the two AOM doses and extending for 42 weeks. Also, one group received 1.25% tea and 1.85% whole milk. The incidence of exophytic or invasive colon cancer and tumor multiplicity were similar in all treatment groups, although the incidence of exophytic neoplasms was higher with 2.5% tea. Thus, chronic administration failed to significantly change the incidence and multiplicity of the AOM-induced colon cancers. These findings are accounted for by the underlying mechanism, namely the fact that tea solutions do not alter the amount of cytochrome P-4502E1 required for the metabolic activation of AOM.

Animals↗
PubMed1998

Effect of tea extracts, polyphenols, and epigallocatechin gallate on azoxymethane-induced colon cancer.

Studies were conducted to determine the chemopreventive efficacy of several types of tea extracts on azoxymethane-induced colon cancer in male F344 rats. After determining the maximally tolerated dosage of the tea products, their effect in a colon cancer model was investigated. Groups of 36 male F344 rats received 2 subcutaneous doses of 15 mg/kg azoxymethane (AOM) at Weeks 6 and 7. Experimental groups also received as drinking fluids 3600 ppm of black or green tea extracts, 1800 ppm of EGCG, or 1800 ppm of black or green tea polyphenols beginning at 5 weeks of age. Additional groups drank a lower dose of 360 ppm of the five tea products. The experiments were terminated 43 weeks after the first tea exposure. No evidence of toxicity was observed since the body weight gain of all groups was similar. The rats given AOM had carcinoma of the small intestine and of the colon, classified histologically as in situ carcinoma, exophytic, invasive, and Peyer's patch carcinoma. In the small intestine, most of the neoplasms were classified as invasive, but in the colon, most were exophytic. The various tea products failed to produce a significant difference in the incidence of the several types of colon and small intestine carcinoma. The multiplicity of colon cancers ranged from 1.2-2.8 in all groups. The group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the control group on AOM and water. Also, the group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the group on 360 ppm. The tea products did not affect the development aspects of the tumors in most groups. The mechanisms underlying these findings rest on the fact that azoxymethane is metabolized mainly by cytochrome P450 2E1, and this enzyme system is not affected by tea.

Animals↗
PubMed1996

Three-year experience with a stylet for lead extraction: a multicenter study.

INTRODUCTION: The extraction of chronically implanted and infected pacemaker and defibrillator leads is an important issue. This article describes the experience gathered between 1990 and 1994 by seven European centers regarding a locking stylet that is uniformly applicable for a wide variety of internal pacing coil diameters. This interventional locking stylet for lead extraction has an outer diameter of 0.4 mm (0.016 inches). The stylet consists of a hollow shaft in which an inner traction wire is embedded. At the tip of the inner traction wire an anchoring mechanism, which can be opened by retraction, is applied. Removal attempts were made for 150 leads, 110 in ventricular and 40 in atrial positions. RESULTS: Complete removal was possible in 122 cases (81%). Partial removal was possible in 18 cases (12%). Failure to remove the lead with the extraction stylet was experienced in 10 cases (7%). In seven patients, the leads were removed by cardiothoracic surgery; 3 defective leads were left in place. There were no serious complications associated with the procedure. None of the patients died. CONCLUSION: The experience with this extraction stylet for lead removal has shown good results. Despite a low complication rate thus far, each case for lead removal should be judged on the individual basis of benefit-to-risk ratio.

Aged↗
PubMed1995

Highly sensitive coupled-column high-performance liquid chromatographic method for the separation and quantitation of the diastereomers of leucovorin and 5-methyltetrahydrofolate in serum and urine.

A column-switching chiral HPLC assay was developed that allows the separation and quantitation of the diastereomers of leucovorin (LV, 5-formyltetrahydrofolic acid) and its metabolite 5-methyltetrahydrofolate (METHF) in serum and urine by means of fluorescence detection. The analysis procedure consists of an on-line concentration of the folates in the HPLC system which is followed by the elution and separation of folates on an achiral 3-microns Microbore C18 column in (6R,S)-LV and (6R,S)-METHF. (6R,S)-LV and (6R,S)-METHF are subsequently transferred on-line onto a chiral 7-microns bovine serum albumin column through a Rheodyne valve system and are separated into their diastereometers. Time of analysis is 70 min. Detection limit is 5 ng/ml for each diastereometer. The within-day variation ranges between 3.2 and 15.8% in relation to the measured concentration. Between-day variation is 4.4-12.1% for a concentration of 100 ng/ml for each diastereometer. (6R,S)-LV and (6S)-LV pharmacokinetics were assessed by analyzing serum and urine samples of four-healthy volunteers.

Antineoplastic Agents↗
PubMed1994

Genotoxicity and carcinogenicity in rats and mice of 2-amino-3,6-dihydro-3-methyl-7H-imidazolo[4,5-f]quinolin-7- one: an intestinal bacterial metabolite of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline.

BACKGROUND: Compounds formed on the surface of fried or grilled meat and fish may be associated with increased risk of colon cancer. Normal intestinal bacteria can convert one of these compounds, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), to the 7-hydroxy metabolite, 2-amino-3,6-dihydro-3-methyl-7H-imidazolo[4,5-f]quinolin-7-o ne (7-OHIQ), a direct-acting mutagen. PURPOSE: We studied the genotoxicity and carcinogenicity of 7-OHIQ to determine if it is responsible for the colon-specific activity of IQ. METHODS: The effects of pure, synthetic 7-OHIQ on DNA were evaluated in the Ames Salmonella typhimurium TA98 test, with and without an induced rat liver S9 fraction, and in the Williams DNA repair test using freshly explanted rat hepatocytes. 7-OHIQ was also subjected to an in vivo bioassay for 21 months by long-term intrarectal infusion in male F344 rats, using IQ and N-nitrosomethylurea (NMU) given intrarectally as positive tumor-producing controls. The standard NIH-07 rodent diet was supplemented with 15% corn oil to maximize any effect of the infused materials on the colon. A parallel bioassay involved intraperitoneal injection of 7-OHIQ in newborn mice, followed by dietary administration from week 11 to week 67. Again, IQ and NMU were used as positive controls. RESULTS: We confirmed that 7-OHIQ is a direct-acting mutagen in the Ames test, with added S9 liver fraction giving higher mutagenicity. 7-OHIQ was negative in the Williams test, whereas IQ was positive. 7-OHIQ did not induce colon cancer in rats, and in the newborn mouse test it produced only a low incidence of liver neoplasms. CONCLUSIONS: 7-OHIQ is not genotoxic, for to be so classified it must be definitely positive in both the Ames and Williams tests; moreover, it is not carcinogenic, in marked contrast to IQ and NMU.

Animals↗
PubMed1994

The role of fat and calcium in the production of foci of aberrant crypts in the colon of rats fed 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine.

The modulation by dietary fat levels of intestine carcinogenesis is well documented. New developments suggest that calcium ions may also play a role. A rapid bioassay, the induction of foci of aberrant crypts in the colon, was used to explore the interaction between dietary fat and calcium. Male F344 rats 6 weeks of age were placed on diets containing 5 or 20% corn oil, and 0.04 or 0.32% calcium ion, as calcium lactate. Each dietary group was fed 400 ppm 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP), and negative controls received the diets alone. A positive control group was given 2 mg N-nitrosomethylurea (NMU) intrarectally four times in a 2-week period. All rats were killed after 9 weeks. The intestinal tract was rinsed with Krebs-Ringer buffer. After staining a 6-cm segment of the descending colon and rectum with 0.2% methylene blue, foci of aberrant crypts were evaluated microscopically. With PhlP as a carcinogen, the rats on a high-fat, low-calcium level had more foci of aberrant crypts than animals on a low-fat level. With the higher calcium level, there were fewer foci and aberrant crypts, but the effect of fat was still significant. With NMU and a low-calcium level, the effect of fat level was evident. However, with the higher calcium intake, there were considerably more foci of aberrant crypts than on the low-calcium level, and the effect of the dietary fat level was not obvious.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Identification of alcoholism and depression in a geriatric medicine outpatient clinic.

OBJECTIVE: To examine the utility of brief screening instruments for alcoholism and depression in the frail elderly medical outpatient. DESIGN: Cross-sectional examination. SETTING: Coffey Geriatric Outpatient Clinic, The Mount Sinai School of Medicine, New York City. SUBJECTS: Convenience sample of 84 consenting male and female outpatients over 62 years of age. MEASUREMENTS: The Michigan Alcohol Screening Test (MAST), CAGE questionnaire, and the Geriatric Depression Scale (GDS). RESULTS: Four subjects (5%) scored positive for alcoholism on the MAST, all of whom had been previously identified by the geriatric clinic staff. In contrast, the CAGE only identified 1 (1.4%) alcoholic subject. Thirty-two percent of subjects scored positive for depression on the GDS, yet only one-third of these depressed patients had been previously identified by the geriatric team as depressed. Among the depressed outpatients, 19% were labeled anxious and received anxiolytics from the geriatric medical staff. CONCLUSIONS: Whereas brief alcohol screening instruments to detect alcoholism did not augment the geriatrician's clinical assessment, screening for depression with the GDS may be an important adjunct to the identification of depression in geriatric medical patients.

Aged↗
PubMed1993

Penetration of Sandimmune (cyclosporin A) in rat skin in vitro. Effects of penetration enhancers and solvents.

The effect of various fatty acids or alcohols on the penetration rates and skin concentrations of cyclosporin A (Sandimmune; CyA) was evaluated in an in vitro model using skin of hairless rats. The influence of chain length, number and position of double bonds and branching of the carbon chain of the enhancer were investigated. In addition the penetration dependency of CyA on the concentration of both enhancer and CyA was studied. CyA was quantitated by high-performance liquid chromatography. The penetration rates of CyA through rat skin decreased with increasing number of double bonds of the enhancer and decreasing CyA concentrations in the donor solution, and increased with increasing chain length of the enhancer. Enhancers increase penetration rates by a factor of up to 20-90 in alcoholic vs. maximally 5-fold in oily compositions. Enhancers increase skin concentrations of CyA by a factor of up to 10-25 in alcoholic and about 4-20 in oily compositions.

Animals↗
PubMed1992

A three-year evaluation of the know your body program in inner-city schoolchildren.

The impact of the Know Your Body (KYB) comprehensive school health education program was evaluated in a sample of first through sixth-grade students from New York City, using two analytic strategies: a longitudinal cohort and a "posttest only" cohort. In both cohorts, program impact was examined between condition (i.e., KYB vs. no-treatment comparison group) as well as within condition (i.e., low, moderate, and high student exposure). Students in the longitudinal cohort (n = 1,209) who were exposed to high implementation teachers had significantly (p < .05) lower total plasma cholesterol and systolic blood pressure at 3-year posttest than comparison students. Students in the posttest only cohort (n = 3,066) who had high implementation teachers showed significantly (p < .05) lower total plasma cholesterol, systolic blood pressure, self-reported intake of meat and desserts, as well as higher health knowledge and self-reported intake of "heart healthy" foods and vegetables than comparison students. In both cohorts, program effects for several outcome variables were linearly related to level of student exposure to the curriculum, suggesting a dose-response effect. While several methodologic limitations may have influenced study outcomes, these data nonetheless appear to confirm that the KYB program can have a significant positive impact on the knowledge, behavior, and selected risk factors of students in primary grades and that efforts to disseminate and evaluate school health education programs should include strategies to monitor and enhance teacher implementation.

Blood Pressure↗